Yilmaz M T, Devrim A S, Biyal F, Satman I, Arioğlu E, Dinççag N, Karsidağ K, Ozden I, Gürel N, Sipahioğlu F
Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, Turkey.
Diabetes Res Clin Pract. 1993 Feb;19(2):151-62. doi: 10.1016/0168-8227(93)90108-h.
This prospective pilot study was undertaken to test the efficacy of oral methyl-prednisolone (MP) therapy at spontaneous remission phase of type 1 diabetes in intervening the course of the disease. Twenty-five type 1 diabetic patients who were classified as having a spontaneous remission (honeymoon) were divided into treatment and non-treatment groups on voluntary basis. Fifteen patients thus making up the treatment group (13 males and 2 females, mean age 23.8 +/- 6.2 years) received 0.7-1.0 mg/kg/day of MP p.o. for 2 weeks. The dose of the drug was then gradually diminished every week until 5 mg/day (approx. 0.1 mg/kg/day) and discontinued at 10 +/- 2 weeks. In case of hyperglycemia occurring in 12 of 15 patients due to the administration of steroid, insulin was used to normalize blood glucose levels (average 0.47 +/- 0.21 IU/kg/day). The non-treatment group (8 males and 2 females, mean age 21.8 +/- 8.9) did not receive any special medication or placebo except for insulin whenever necessary to regulate glycemia. Upon completion of protocol, all patients in treatment group displayed clinical remission with 10 still in non-insulin requiring remission for follow-up periods ranging between 16 and 91 months. The remaining 5 patients relapsed within 3-15 months of therapy. Other metabolic (including basal and stimulated C-peptide levels) and immunological indices that have spontaneously ameliorated with the occurrence of honeymoon were also maintained within normal range in the NIR patients. Meanwhile, natural remission in the non-MP-treated group terminated at 3.4 +/- 0.6 months with deterioration of all metabolic and immunological markers as well as increasing requirements for insulin. In conclusion, the spontaneous remission of the patients could be prolonged significantly by MP therapy as opposed to no therapy (P < 0.001). These results suggest that the spontaneous remission phase may be a crucial point of intervention in immunotherapy of type 1 diabetes and that randomized trials with MP at this particular phase would be worthwhile.
本前瞻性试点研究旨在测试口服甲基泼尼松龙（MP）疗法在1型糖尿病自发缓解期对干预疾病进程的疗效。25名被归类为处于自发缓解期（蜜月期）的1型糖尿病患者自愿分为治疗组和非治疗组。治疗组由15名患者组成（13名男性和2名女性，平均年龄23.8±6.2岁），口服MP 0.7 - 1.0mg/kg/天，持续2周。然后每周逐渐减少药物剂量，直至5mg/天（约0.1mg/kg/天），并在10±2周时停药。15名患者中有12名因使用类固醇出现高血糖，使用胰岛素使血糖水平正常化（平均0.47±0.21IU/kg/天）。非治疗组（8名男性和2名女性，平均年龄21.8±8.9岁）除必要时使用胰岛素调节血糖外，未接受任何特殊药物或安慰剂治疗。方案完成后，治疗组所有患者均出现临床缓解，其中10名患者在随访期16至91个月内仍处于无需胰岛素治疗的缓解状态。其余5名患者在治疗3至15个月内复发。蜜月期出现自发改善的其他代谢指标（包括基础和刺激后的C肽水平）以及免疫指标在近正常血糖患者中也维持在正常范围内。同时，未接受MP治疗组的自然缓解在3.4±0.6个月时终止，所有代谢和免疫标志物均恶化，胰岛素需求增加。总之，与不治疗相比，MP治疗可显著延长患者的自发缓解期（P<0.001）。这些结果表明，自发缓解期可能是1型糖尿病免疫治疗的关键干预点，在此特定阶段进行MP的随机试验是值得的。
